DESCRIPTION (Adapted from the application): The goal of the proposed research is to develop an efficacious radiotherapeutic agent for the treatment of malignant melanoma. A rhenium cyclized alpha-melanocyte stimulating hormone (alpha-MSH) analog ReCCMSH will be used to target melanoma tumors with the alpha particle emitting radiometal Bi-212, or its parent isotope Pb-212. The ReCCMSH peptide has a high affinity for alpha-MSH receptors present on melanoma cells and is rapidly internalized upon binding. ReCCMSH will be conjugated to the DOTA metal chelate and radiolabeled with Pb-212. The parent Pb-212[(DOTA)-ReCCMSH] complex will be used as an in vivo Bi-212[DOTA-ReCCMSH] generator, due to the short half-life of Bi-212. Both the Pb-212- and Bi-212[DOTA-ReCCMSH] molecules will be examined for their radiochemical stabilities and alpha-MSH receptor affinities in vitro and for their biodistribution and tumor targeting properties in vivo. The incidence of malignant melanoma is on the rise. Malignant melanoma is resistant to conventional chemo- and external beam radiation therapy. Selective delivery of a high-energy, short path length, alpha-particle-emitting radiometal to melanoma cells will yield a lethal dose to the tumor while reducing collateral exposures of vital organs and tissues. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE